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. 2021 Jun 19;24(7):102759. doi: 10.1016/j.isci.2021.102759

Figure 1.

Figure 1

Combination of oHSV with anti-PD-1 antibody significantly prolongs survival in K7M2 tumor model but does not prolong survival in F420 tumor model

(A) Schematic illustrates the dosing regimens.

(B) F420 tumor volumes of mice treated with PBS (black line; n = 5), oHSV (red line; n = 5), anti-PD-1 (blue line; n = 5), and combination therapy (green line; n = 5). Mice were measured twice per week.

(C) F420 tumor model Kaplan-Meier survival curves for each treatment group. Survival data were evaluated for statistical significance with Log rank Mantel-Cox test and for tumor size in panel f with two-way ANOVA (n = 4 mice per group; ∗p ≤ 0.05).

(D) K7M2 tumor volumes of mice treated with PBS (black line; n = 5), oHSV (red line; n = 4), anti-PD-1 (blue line; n = 5), and combination therapy (green line; n = 6). Mice were measured twice per week.

(C) F420 tumor model Kaplan-Meier survival curves for each treatment group.

(E) K7M2 tumor model Kaplan-Meier survival curves for each treatment group demonstrating efficacy of combination therapy. Survival data were evaluated for statistical significance with Log rank Mantel-Cox test and for tumor size in panel f with two-way ANOVA (n = 4 mice per group; ∗p ≤ 0.05).

(F) Average tumor growth curves of mice treated as in Figure 1A but with IP administration of CD4 or CD8 T cell depleting or control antibodies every four days starting at day −1. Error bars represent standard deviation of the mean.

(G) Cell viability assay at varying MOI of HSV1716 on K7M2 (open triangle) versus F420 (closed square) at Day 3. Error bars represent standard deviation of the mean.

(H) Viral replication assay of F420 (black) and K7M2 (white) with HSV1716 MOI 0.1 at hr 2, 24, 48, and 72. Samples were run in 3 samples per time period with each sample run in triplicate for 9 samples per time period. Error bars represent standard deviation of the mean. Survival data were evaluated for statistical significance with Log rank Mantel-Cox test and for tumor size in panel f with two-way ANOVA (n = 4 mice per group; ∗p ≤ 0.05). ITu: intratumoral; PBS: phosphate-buffered solution; IP: intraperitoneal; anti-PD-1: anti-programmed death 1; ab: antibody; MOI: multiplicity of infection (pfu/cell); pfu: plaque-forming units.